ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1039C>T (p.Arg347Cys) (rs397508147)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000729383 SCV000857039 uncertain significance not provided 2017-09-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780155 SCV000917202 uncertain significance not specified 2018-05-04 criteria provided, single submitter clinical testing Variant summary: CFTR c.1039C>T (p.Arg347Cys) results in a non-conservative amino acid change located in a transmembrane domain (IPR011527) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 245910 control chromosomes. This frequency is not higher than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (1.2e-05 vs 0.013), allowing no conclusion about variant significance. The variant, c.1039C>T, has been reported in the literature in individuals affected with Cystic Fibrosis (Koch 2001, Ravnik-Glavac 2002), however the exact phenotype and the variants found in trans were not specified. A CFTR locus specific database (CFTR-France) lists the variant to be found in an individual affected by CFTR-RD (bronchiectasis). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, demonstrating defective conductance, however, this report does not allow convincing conclusions about the variant effect (Cotton 1999). Other variants affecting the same amino acid position (Arg347Pro, Arg347His) are reported as well known disease variants. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577686 SCV000678880 not provided Cystic fibrosis no assertion provided literature only

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